Differential Effects of Distinct Type I Interferons and IFN Inducers on Fc Receptor landscape and myeloid cell function
Abstract
Antiviral monoclonal antibodies (mAbs) rely on Fc-mediated effector functions, which depend on interactions with Fc receptors (FcRs) expressed on immune cells such as monocytes and dendritic cells (DCs). While combinations of antiviral mAbs with type I interferons (IFN-I) or IFN inducers are being explored to enhance therapeutic efficacy, the impact of these immunomodulators on FcR expression remains poorly understood. In this study, we investigated the effects of IFN-α2, IFN-β, and the IFN-inducer TAK-981 (a SUMOylation inhibitor) on FcR modulation and functional activation in human monocyte subsets and monocyte-derived DCs (moDCs). Using flow cytometry and imaging techniques, we mapped the expression of activating FcγRs (CD64, CD32A, CD16A) and neonatal FcR (FcRn) under steady-state and stimulated conditions. We found that IFN-I selectively downregulates CD16A expression in classical monocytes while preserving other FcRs, whereas TAK-981 reduces FcRn expression in classical monocytes without affecting CD16A. Additionally, IFN-β and TAK-981 but not IFN-α2, selectively enhanced FcγRI expression in moDC. IFN-β also induced a stronger maturation and functional activation program in monocytes and moDCs compared with IFN-α2, whereas TAK-981 largely reproduced the IFN-β-driven phenotype and secretory profile. Furthermore, we demonstrated that IFN-I signaling alters the spatial distribution of FcRs, with IFN-β and TAK-981 promoting distinct redistribution patterns of FcγRs in monocytes and moDCs. These findings reveal a novel layer of FcR regulation, highlighting that IFN-I and IFN inducers differentially modulate FcR expression, localization, and functional activation in a cell-type- and stimulus-specific manner. Overall, this work provides a framework for understanding how IFN-I-based immunotherapies may influence Fc-mediated immune functions while preserving FcRn-dependent antibody persistence.
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BibTeX
@misc{bru2026differential,
title = {{Differential Effects of Distinct Type I Interferons and IFN Inducers on Fc Receptor landscape and myeloid cell function}},
author = {Rémi Bru and Océane Paris and Guillaume Bossis and Stephanie Boireau and Mar Naranjo-Gomez and Mireia Pelegrin},
howpublished = {HAL},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.756027},
url = {https://hal.science/hal-05841901v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - Differential Effects of Distinct Type I Interferons and IFN Inducers on Fc Receptor landscape and myeloid cell function
AU - Rémi Bru
AU - Océane Paris
AU - Guillaume Bossis
AU - Stephanie Boireau
AU - Mar Naranjo-Gomez
AU - Mireia Pelegrin
PY - 2026
DA - 2026/10/01
PB - HAL
DO - 10.64898/2026.10.01.756027
UR - https://hal.science/hal-05841901v1
AB - Antiviral monoclonal antibodies (mAbs) rely on Fc-mediated effector functions, which depend on interactions with Fc receptors (FcRs) expressed on immune cells such as monocytes and dendritic cells (DCs). While combinations of antiviral mAbs with type I interferons (IFN-I) or IFN inducers are being explored to enhance therapeutic efficacy, the impact of these immunomodulators on FcR expression remains poorly understood. In this study, we investigated the effects of IFN-α2, IFN-β, and the IFN-inducer TAK-981 (a SUMOylation inhibitor) on FcR modulation and functional activation in human monocyte subsets and monocyte-derived DCs (moDCs). Using flow cytometry and imaging techniques, we mapped the expression of activating FcγRs (CD64, CD32A, CD16A) and neonatal FcR (FcRn) under steady-state and stimulated conditions. We found that IFN-I selectively downregulates CD16A expression in classical monocytes while preserving other FcRs, whereas TAK-981 reduces FcRn expression in classical monocytes without affecting CD16A. Additionally, IFN-β and TAK-981 but not IFN-α2, selectively enhanced FcγRI expression in moDC. IFN-β also induced a stronger maturation and functional activation program in monocytes and moDCs compared with IFN-α2, whereas TAK-981 largely reproduced the IFN-β-driven phenotype and secretory profile. Furthermore, we demonstrated that IFN-I signaling alters the spatial distribution of FcRs, with IFN-β and TAK-981 promoting distinct redistribution patterns of FcγRs in monocytes and moDCs. These findings reveal a novel layer of FcR regulation, highlighting that IFN-I and IFN inducers differentially modulate FcR expression, localization, and functional activation in a cell-type- and stimulus-specific manner. Overall, this work provides a framework for understanding how IFN-I-based immunotherapies may influence Fc-mediated immune functions while preserving FcRn-dependent antibody persistence.
ER -